Regensburg 2016 – wissenschaftliches Programm
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BP: Fachverband Biologische Physik
BP 44: Biotechnology & Bioengineering
BP 44.5: Vortrag
Mittwoch, 9. März 2016, 16:15–16:30, H45
GALA - A cell penetrating peptide with a trigger — Johannes Franz1, Denise Schach1, Will Rock1, Christoph Globisch2, Steven Roeters3, Sander Woutersen3, Christine Peter2, Mischa Bonn1, Sapun Parekh1, and •Tobias Weidner1 — 1MPI für Polyerforschung, Mainz, Germany — 2Universität Konstanz, Germany — 3University of Amsterdam, The Netherlands
Cell-penetrating peptides are promising for drug delivery into cells. Since the cell uptake mainly involves endocytic mechanisms, the enclosure of peptides within endosomes is still an unresolved challenge for biomedical applications * the peptide and its cargo are trapped in the *recycling bin* of the cell. The peptide GALA, a viral fusion mimic is triggered by pH, and takes advantage of the decreasing pH during endosome maturation to selectively attack endosomal membranes. Below pH 6, the sequence folds into a helix and disrupts biomembranes. We used surface specific sum frequency generation (SFG) spectroscopy jointly with fluorescence imaging and molecular dynamics simulations to study GALA in action at interfaces. We show that the lipid bilayer radius-of-curvature has a negligible effect on GALA-induced membrane leakage and that GALA remains pH responsive after inserting into a lipid membrane. The peptide can be reversibly *switched* between its inactive and active states after incorporation into the hydrophobic environment of lipid membranes, even after substantially interacting with lipid chains. GALA-based delivery is a potentially safe, effective route towards effective endosomal escape strategies. JACS 137, 12199*12202 (2015); ChemComm 51, 273-275 (2015); JCP 141, 22D517 (2014).